Impact of the change in the antitubercular regimen from three to four drugs on cure and frequency of adverse reactions in tuberculosis patients from Brazil: A retrospective cohort study

Abstract

BackgroundThe Ministry of Health in Brazil included ethambutol in the intensive phase of sensible tuberculosis (TB) treatment in March 2010, due to the increasing drug resistance, and implemented the fixed dose combination in the TB treatment guidelines.MethodsA retrospective cohort study was performed to determine the impact of change from three to four drugs schemes on the TB cure and frequency of adverse drug reactions (ADRs) in TB patients. To answer this question, we used data from 730 randomly selected patients who received anti-TB treatment between January 2007 and December 2014 in a reference center from Salvador, Brazil.FindingsTB patients who received the RHEZ regimen (n = 365) developed ADRs more frequently than those treated with the RHZ (n = 365) (86 [23.6%] vs. 55 [15.1%]; p = 0.01). This difference in ADR incidence was even higher in patients above 30 years-old (64 [74.4%] vs. 36 [65.5%]; p = 0.01). The overall number of ADR episodes was greater in patients from the RHEZ group than in the group that received RHZ (170 [61.4%] vs. 107 [38.6%]; p = 0.03). Multivariable logistic regression analysis adjusted for age, alcohol use and diabetes demonstrated that patients receiving the RHEZ regimen had increased odds of developing ADRs than those undertaking the RHZ scheme (odds ratio [OR]: 1.61, 95% confidence interval [CI]: 1.10–2.35; p = 0.015). The overall cure rate was similar between the distinct treatment groups.ConclusionThe patients treated with the four-drug regimen exhibited increased risk of ADRs compared to those who received the three-drug regimen, and especially in patients older than 30 years of age.

Prediction Models for Adverse Drug Reactions During Tuberculosis Treatment in Brazil

“…We selected the candidate predictors for the two prediction models incorporating information from a comprehensive literature review and biological plausibility. [20][21][22][23][24][25] Considerable deliberation was given to the inclusion of the following variables: CM use, HIV status (positive or negative), HbA1c, age, body mass index (BMI), alcohol use, tobacco use, drug use, sex, and the genetic data.…”

Impact of adverse drug reactions on the outcomes of tuberculosis treatment

“…Retrospective studies conducted in Brazil found an incidence of ADR between 23% to 83% [5][6][7] and in a meta-analysis including other non-Brazilian studies, the incidence varied from 8.4% to 83.5% [8]. ADRs are multifactorial [9,10] and the major determinants are unadjusted prescribed doses of medications, patient's age, nutritional status, alcohol consumption, altered liver and kidney function and HIV-infection [11,12].…”

“…ART during ATT is challenging because of drug-to-drug interactions and increased risk of ADR. In Brazil there are few studies on ADR during ATT [5][6][7] correlating with outcomes. To the best of our knowledge, there are no studies to date including ADR during ATT in PLHIV.…”

Impact of Adverse Drug Reactions in the outcomes of Tuberculosis Treatment

“…The ATT recommended by World Health Organization (WHO) and implemented since 2009 in the Brazilian guidelines is as a fixed-dose (FDC), single-tablet combination of four drugs (rifampicin, isoniazid, pyrazinamide, and ethambutol) during the intensive phase of treatment followed by rifampicin and isoniazid in FDC until the end of treatment [4] Retrospective studies conducted in Brazil found an incidence of ADR between 23% to 83% [5][6][7] and in a meta-analysis including other non-Brazilian studies, the incidence varied from 8.4% to 83.5% [8]. ADRs are multifactorial [9,10] and the major determinants are unadjusted prescribed doses of medications, patient's age, nutritional status, alcohol consumption, liver and kidney function and HIV-infection [11,12].…”